1. Field of the Invention
The present disclosure in general relates to the field of osteoporosis treatment. More particularly, the present disclosure relates to a method of treating osteoporosis by use of a neddylation inhibitor.
2. Description of Related Art
Osteoporosis is a disorder characterized by low bone density, which is an important risk factor for bone fracture in older adults. Osteoporosis is more common in women than men. In developed countries, approximately 2-8% males and 9-38% females are diagnosed with osteoporosis. Osteoporosis does not in itself cause any symptom to the subject, except an increased risk of bone fractures. Osteoporotic fractures usually occur in situations where healthy people would not normally break a bone. Typical osteoporotic fractures include hip, vertebral, wrist and rib fractures.
The differentiation and activation of osteoclasts from the monocyte/macrophage hematopoietic lineage is majorly mediated by receptor activator of nuclear factor kappa-B ligand (RANKL) signaling on normal bone matrix remodeling. The over-activation of osteoclasts secretes acid and lytic enzymes that degrade bone matrix can result in osteolytic bone diseases and osteoporosis. Therefore, targeting the differentiation and functional activity of osteoclasts have afforded insights into the means of osteoclastogenesis and activation of bone resorption for developing the potential therapies on treating osteoporosis and other diseases of bone loss.
It has been reported that bone loss increases after menopause due to lower levels of estrogen. In addition, several factors also contribute to the development of osteoporosis, including alcoholism, caffeine, tobacco smoking, vitamin D deficiency, malnutrition, heavy metal (e.g., cadmium and lead), hyperthyroidism, kidney disease, and medication (e.g., aromatase inhibitors, methotrexate, proton pump inhibitor, and steroid etc.).
Smoking cessation, moderate intake of alcohol intake and specific supplements (such as calcium and vitamin D) are reported to be useful in the prevention of osteoporosis. As to the medications, bisphosphonate (a class of drugs for preventing the loss of bone mass), estrogen (also known as oestrogen, the primary female sex hormone associated with bone deposition), Teriparatide (a recombinant parathyroid hormone with effect on stimulating the formation of new bone and restoring lost bone mass), Raloxifene (an estrogen receptor modulator having effect on reducing the level of bone metabolism), Denosumab (a monoclonal antibody inhibitor of receptor activator of nuclear factor κ-B ligand (RANKL) on suppressing the development of osteoclasts), Calcitonin (a calcium regulatory hormone, strongly inhibiting bone-resorbing activity of osteoclast), and strontium ranelate (a strontium(II) salt of ranelic acid, stimulating the formation of new bone tissue and decreasing bone resorption) provide potential means to treat osteoporosis and/or osteolytic diseases. However, each of therapeutic approaches listed above has its limitation. For example, bisphosphonate usually causes abdominal pain, nausea, vomiting, dyspepsia, musculoskeletal pain and osteonecrosis of the jaw. Estrogen may increase the risk of heart attack, blood-clot formation, stroke, endometrial hyperplasia and breast and endometrial cancers. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps and dizziness. Raloxifene may increase the risk of blood-clot formation and stroke. Denosumab may result in hypocalcemia and steonecrosis of the jaw; further, it also compromises the immune response to microorganism infection. Calcitonin is associated with allergy and the development of difference cancers. Regarding strontium ranelate, it may cause nausea, diarrhea, headache, seizures, memory loss and consciousness disturbances.
In view of the foregoing, there exists in the related art a need for a novel method of safely and effectively preventing and/or treating abnormal bone resorption and/or osteoporosis so as to improve the life quality and life span of the subject in need thereof.